Israel Medical Association Journal

Contactin associated protein-like 2 (CASPR2) and leucine-rich glioma-inactivated protein 1 (LGI1) voltage gated potassium channel (VGKC) proteins are found in both the central and peripheral nervous systems [1]. Antibodies against these proteins are associated with encephalopathy, seizures, peripheral nerve hyper-excitability, autonomic dysfunction, hyponatremia, pain, and insomnia in varying severity and combination [1].

Morvan syndrome, first described in 1890, combines symptoms of peripheral nervous system (PNS), central nervous system (CNS), and autonomic nervous system dysfunction. It was later found to be associated with VGKC-complex antibodies, mainly against CASPR2 or LGI1 or both.

Our patient had a history of anti-LGI1 positive limbic encephalitis, which presented years later with anti-CASPR2 positive Morvan syndrome.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

Metastatic pulmonary calcinosis (MPC) is characterized by deposits of calcium in normal pulmonary parenchyma. Diffuse pulmonary calcinosis commonly occurs in hypercalcemia and/or hyperphosphatemia and is more commonly related to renal failure than primary hyperparathyroidism, skeletal metastases, or multiple myeloma [1]. Calcium depositions favor alkaline tissue and are thus more common in the upper lobes of the lung, which have a higher ventilation to perfusion ratio and a low capillary pCO₂, resulting in an alkaline pH [2]. Therefore, the most common radiographic manifestation consists of poorly defined nodular opacities bilaterally in the upper lung zones [3].

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Ruxolitinib is an inhibitor of the cytosolic tyrosine kinase Janus kinase (JAK) family of proteins (JAK1/2), which is widely used to treat various myeloid neoplasms that are characterized by constant activation of the JAK-STAT signaling pathway.

Many side effects are associated with ruxolitinib, including anemia, thrombocytopenia, increased rate of infections (especially herpes zoster), and mild hypercalcemia noted in 15.4% of patients [1]. The possible mechanism causing hypercalcemia may involve altered bone and mineral metabolism with secondary hyperparathyroidism, as described for other kinase inhibitors [2].

Familial spastic paraparesis is a non-progressive disorder. However, clinical experience shows that after trauma, disease, surgery, or limb fracture that force a patient's long immobilization, a significant functional deterioration is observed. I describe two patients with Silver syndrome who experienced such functional deterioration after sustaining a simple fracture. A description of Silver syndrome and a biographical sketch of Dr. Silver, who explained the disorder in 1966, are given.

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

The health of survivors of the Shoah has been investigated, both at early and late stages in their lives. There have been findings of multiple morbidities, but survivors have enjoyed slightly prolonged longevity when compared to the general population [1]. Less attention has been granted to investigations and descriptions of illnesses that presented inside the ghettos and the Nazi camps. Some of the surviving records from those sites have yet to be interpreted. Documented diagnoses of both insulin dependent and mature onset diabetes mellitus and of malignancy has been conspicuously absent. We present our meta-analysis and interpretations of surviving medical documents covering a large population of prisoners from a range of ghettos and concentration camps and specifically note the absence of recorded incidence of malignancy and a relatively low incidence of diabetes mellitus.

Background: Myalgic encephalomyelits/chronic fatigue syndrome (ME/CFS) is an acquired disease with symptoms of fatigue and pain. In pathogenesis, the induction of autoantibodies (AAB) against G-protein coupled receptors (GPCR), such as β-adrenergic receptors (β-AdR), has been suspected. GPCR-AAB correlate with symptom severity and autonomic dysfunction in ME/CFS.

Objectives: To describe symptoms and treatment of a patient presenting with infection-triggered ME/CFS demonstrating that levels of β-AdR-AAB underlie modulation over time, correlating with the severity of symptoms.

Methods: At T1 and T2, GPCR-AAB were measured and questionnaires assessing symptom severity were completed. TSHDS-IgM-AAB were tested, and SF density was analyzed via skin probe.

Results: At T2, elevated levels of β-AdR-AAB were found, corresponding with an aggravation of fatigue and pain symptoms. Elevated TSHDS-IgM-AAB were found, which corresponded with reduced fiber density from the skin probe.

Conclusions: The levels of β-AdR-AAB in post-infectious ME/CFS can be modulated. Future studies might target interventions to reduce these AAB.

Background: Children with forearm fractures who present to the emergency department (ED) often need a closed reduction. In our institution, until 2017, pediatric trauma patients presented to the general trauma ED (GTED) where no sedation services for pediatric patients were available. From 2017, patients presented to the pediatric emergency department (PED) where closed reductions were performed under sedation when appropriate.

Objectives: To compare GTED and PED with regard to length of stay (LOS) and hospitalization rates of pediatric patients with forearm fractures who needed a closed reduction.

Methods: Our retrospective observational study was conducted at a regional hospital. The study population consisted of all patients younger than 18 years of age who presented to the ED with a forearm fracture that needed a closed reduction. The primary outcome measure was the hospitalization rate. The secondary outcome measure was LOS in the ED.

Results: The study comprised 165 patients with forearm fractures who needed a closed reduction; 79 presented to the GTED, and 96 presented to the PED. Hospitalization rates were lower for patients undergoing closed reduction under sedation in the PED compared to the GTED (6.3% and 21.5%, respectively; P = 0.003). Median ED LOS was longer among patients undergoing sedation in the PED compared to the GTED (237 vs. 168 minutes respectively, P < 0.0001).

Conclusions: Sedation for forearm fracture reduction in a hospital’s PED was associated with a decrease of more than three times in hospitalization rate. Despite the need for more resources, PED LOS was only mildly increased.

Background: In developed countries, amblyopia has an estimated prevalence rate of 1–4%, depending on the socioeconomic gradient. Previous studies performed on pediatric populations in Ethiopia demonstrated amblyopia rates up to 16.7.

Objectives: To assess rates of amblyopia, refractive errors, strabismus, and other eye pathologies among Ethiopian-born children and adolescents who immigrated to Israel compared to Israeli-born children.

Methods This observational cross-sectional study included children and adolescents 5–19 years of age who immigrated to Israel up to 2 years before data collection and lived in an immigration center. Demographic data and general health status of the children were obtained from the parents, and a comprehensive ophthalmologic examination was performed. Results were compared to Israeli-born children.

Results: The study included 223 children and adolescents: 87 Ethiopian-born and 136 Israeli-born. The rate of amblyopia in the Ethiopian-born group vs. Israeli-born was 3.4% and 4.4%, respectively. Even after controlling for age, there was still no significant difference between the two groups (P > 0.99).

Conclusions: Despite originating from a country with limited resources and fewer medical facilities, the amblyopia rate in Jewish Ethiopian immigrants was not higher, and even mildly lower, compared to Israeli-born children.

Background: The global refugee crises have raised concerns among medical communities worldwide; nonetheless, access to healthcare has rarely been studied even though refugees are a medically high-risk group.

Objectives: To compare pediatric department admission rates from the pediatric emergency department (PED) of refugees and Israelis.

Methods: We compared data from refugee and Israeli children admitted to the pediatric department at Wolfson Medical Center in Israel between 2013–2017.

Results: A total of 104,244 patients (aged 0–18 years) came to the PED. Admission rate to the pediatric department for refugees was 695/2541 (27%) compared to 11,858/101,703 (11.7%) Israeli patients (P < 0.001). Hospital stay for patients 0–2-years of age was 3.22 ± 4.80 days for refugees vs. 2.78 ± 3.17 for Israelis (P < 0.03). Re-admission rate within 7 days was 1.3% for refugees and 2.6% for Israelis (P < 0.05). Dermatological diseases (e.g., impetigo and cellulitis) were more frequent in refugees (23.30% vs. 13.15%, P < 0.01); however, acute gastroenteritis and respiratory diagnoses were more common in Israelis (18.52% vs. 11.72%, P < 0.05 and 14.84% vs. 6.26%, P < 0.01, respectively). Neurological diseases (e.g., febrile convulsions) were also more frequent in Israelis (7.7% vs. 3%, P < 0.05). Very significantly, 23% of refugees had no healthcare coverage, while only 0.2% of the Israelis had none (P < 0.001).

Conclusions: We found significant morbidity in refugees compared to the local Israeli pediatric population, highlighting the need for different approaches for each population.

Background: Physiotherapy can help treat of trigger fingers (TF).

Objectives: To compare efficacy of fascial manipulation (FM) and traditional physiotherapy (TP) techniques in treatment of TF.

Methods: Nineteen patients were randomized in the FM group and 15 in the TP group. All patients underwent eight physiotherapy sessions. The Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and visual analogue scale (VAS) scores, staging of stenosing tenosynovitis (SST) classification, triggering frequency, grip and pinch strength were recorded before and after treatment. We surveyed participants at 6 months for recurrence, further treatment, and the VAS and QuickDASH scores. The primary outcome measure was reduction in QuickDASH and VAS scores.

Results: Both FM and TF improved the QuickDASH and VAS scores at 6 months follow-up, without a significant difference. The QuickDASH score in the FM group improved from 28.4 ± 17.1 to 12.7 ± 16.3; TF scores improved from 27 ± 16.7 to 18.8 ± 29.4 (P = 0.001). The VAS score improved from 5.7 ± 2.1 to 1.2 ± 2.1 and from 4.8 ± 1.8 to 2 ± 2.6 for both groups, respectively (P < 0.001). SST and grip strength also improved following treatment, regardless of modality. At 6 months, four patients (22%) with an SST score of 1, three (30%) with a score of 2, and two (40%) with a score of 3A underwent additional treatment.

Conclusions: Both FM and TP techniques are effective for the treatment of TF and should be considered for patients who present with SST scores of 1 or 2.

Background: The two cerebral hemispheres influence the immune response differently. While the left hemisphere enhances cellular immunity, the right hemisphere inhibits it.

Objectives: To determine whether immune and inflammatory markers correlated with stroke severity and hospitalization duration as a function of stroke side.

Methods: The study included 137 patients with unilateral ischemic stroke. The medical records were reviewed for demographic and clinical laboratory data, including C-reactive protein (CRP), white blood cell (WBC) count, its differential stroke side and stroke severity according to the National Institute of Health Stroke Scale (NIHSS), and length of hospital stay (LOS). We examined differences between right side (RS) and left side (LS) stroke on immune and inflammatory markers and compared correlations between these markers and NIHSS and LOS as a function of stroke side.

Results: RS stroke patients had higher CRP and monocytes than LS stroke patients. In RS stroke patients, CRP, total WBC, and lymphocyte levels positively correlated with both NIHSS and LOS, whereas levels of neutrophils were positively correlated with NIHSS alone. No correlations were found for LS stroke patients.

Conclusions: Immune-inflammatory markers correlated with stroke severity and LOS only in patients with RS stroke. Neuroimmunological processes influence short-term clinical outcomes after stroke, especially considering the differential effects of the hemispheres on immunity. Prospective studies that evaluate long-term clinical outcomes are needed. Testing the effects of anti-inflammatory treatments on prognosis of RS stroke patients should be considered.

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.